Potential risks of using Bempedoic acid and Ezetimibe for anti-aging?

#1

Hey fellow biohackers,

I wanted to introduce myself and share my background. I’m 23, and while I’ve been lurking on this forum for a few months, I actually started a heavy longevity supplement protocol when I was 20. That includes Rapamycin. I was initially pretty terrified of the side effects—specifically testicular atrophy and fatty liver seen in mouse models—but what finally sold me was Dr. Alan Green’s interviews and digging through the literature. It seems clear that intermittent dosing is the key to dodging those downsides.

I’m posting today because I need some help. I’ve noticed a lot of people here taking Bempedoic Acid and Ezetimibe. To be honest, I hadn’t heard of these being used in a longevity context before, so I’m really grateful for the insights this community provides.

I understand that the Bempedoic/Ezetimibe combo is great for lowering cholesterol and reducing the risk of a first cardiovascular event, but I’m worried about the trade-offs. I previously considered statins, but since they can promote vascular calcification, they seem like a better deal for middle-aged folks than for someone my age.

Similarly, I’ve stayed away from Aspirin because mouse data suggests it lowers Klotho levels[https://www.nature.com/articles/s43587-023-00468-0.pdf], which isn’t great for cognitive health. Plus, the research I’ve seen shows no real benefit for dementia prevention—some studies even suggest it might increase the risk[https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.14389]. Again, not a win for someone in their early 20s.

My question is: Can individuals with normal cholesterol levels preemptively take Bempedoic Acid and Ezetimibe for anti-aging purposes? Are there potential benefits to this approach, and what are the potential risks (similar to the risks associated with statins and aspirin mentioned above)?

#2

Just to be clear, I have no intention of causing panic among people taking aspirin or statins. These risks apply specifically to younger populations and the evidence remains extremely limited. I am only using these examples to illustrate that the help I’m seeking is focused on these types of nuanced details.

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#3

Statins only promote vascular calcification if you already have plenty of soft plaque in your arteries. At it’s not promoting it per se as much as stabilizing the plaque. And plenty of studies even show regression of soft plaque to some degree.
They don’t have great evidence in young people because young people don’t usually die from heart attacks.

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#4

According to [Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms - PubMed], statins inhibit the synthesis of Vitamin K2, thereby reducing Matrix Gla Protein (MGP) levels. Simultaneously, they inhibit the biosynthesis of selenoproteins, which can accelerate vascular calcification. I am uncertain whether exogenous supplementation of Vitamin K2 and selenium can effectively counteract these specific side effects.

Furthermore, according to [Checking your browser - reCAPTCHA], even after adjusting for cholesterol levels and other risk factors, the annual progression rate of arterial calcification remains higher in statin users than in non-users.

Here we find a significant association between duration of statin therapy and total CACS. Specifically, long-term duration of statin therapy was significantly associated with a greater risk of having severe CACS. The increasing odds of having severe CACS being associated with higher duration of time on statin therapy remained significant after adjustment for the baseline cardiovascular risk factors known to significantly impact the CACS (ASCVD risk score, BMI, and CKD).

I’m not very familiar with the blockquote feature, so I apologize if the formatting is a bit messy.

#5

You can just supplement with vitamin K2, you know. But studies so far have shown that even without statins, vitamin K2 fails to slow calcifation rates Despite hopes, vitamin K2 supplements fail to slow calcium buildup in heart valve | American Heart Association
The “study” in question you posted is not a study btw, it is a perspective. We had a thread regarding this topic Statins stimulate atherosclerosis and heart failure: pharmacological mechanisms

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#6

Welcome @Cole,

What is the specific goal for which you are considering a BA/Ez combo? If your Apo(b), Lp(a), and inflammation metrics are all in the general area of optimal, I see little need for adding this combo at your age, especially in contrast to other steps you can take, achieving or maintaining high levels of fitness being one of the most significant. Thinking specifically about rapamycin, there is no high quality evidence (RCT or equivalent) that it confers longevity benefits to humans. Of the little human evidence we have, none applies to people your age.

Top line geroprotection for most people your age includes a broad base of fitness, low BP (especially low lability), a genuinely rewarding network of friends, and a meaningful stress managed life. Together, these factors account for almost all of the variance. Avoiding pollution and not drinking alcohol, might also be helpful. Two decades from now, when more targeted geroprotectives might make sense for you, the scientific and clinical communities – aided by pioneers you see here – will have developed better interventions based on a stronger and more coherent base of knowledge.

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#7

There is some evidence that a combination of both forms of K2 and Natto slow the rate of intima thickening but the most promising as of a year or so ago was a single Chinese study.

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#8

I totally agree on this. However, my observation is among my circle of close friends, family, and social groups, such as church members, this is not going to happen. Perhaps one of the reasons for the high rate of CVD among young adults. There are a large percentage of people, I would guess, in big cities, who live in apartments and won’t be going to the gym or running on a regular basis.

I go to thrift stores occasionally to pick up bargain tools, and I always see a lot of home gym equipment, such as treadmills, stationary bikes, and weights.
This indicates to me that many people buy exercise equipment to use at home and do not use it.
I have been guilty of this myself. For me, for some reason, I really prefer to go to the gym.
The point is, we need to find alternatives for shut-ins and other people who do not have the opportunity to go to gyms, etc. We need to find exercise mimetics and caloric restriction mimetics, and other drugs to compensate for the lack of exercise.

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#9

“. . . for some reason, I really prefer to go to the gym.”

We are alike in this. I’m not certain why but I am less likely to skip a gym workout and I work out harder in a gym than I have in my home gyms, a few of which were decently equipped (so it is not the equipment). Neither is it crowd motivation. I belong to a 24/7 gym in Arizona and am occasionally the only person there. Great workouts and no waiting for a machine.

My take is that the interactions among individual differences in genetics and lifestyles are more complex than we have yet to model. I can think of a few people who have been overweight their entire life, eat steak and eggs on a regular basis, and have never seen the inside of a gym or track, yet live well into advanced years. I’m certain I would be dead long before now had I lived their lifestyles.

I think we have yet to identify all or even most of the causal nexi for life-taking diseases. Among the many people in my family who lived healthy lives into their 90’s, I don’t think any had good lipid metrics. My uncorrected LDL/Apo(b) is also high. Yet, no one going back a few generations or sideways to all first cousins, aunts and uncles has had a heart attack, much less died of ASCVD. Of course, I could be the first :slight_smile:

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#10

The key issue here is what are your current lipid measurements (APO-B, LDL-C, LP(a))? don’t just take drugs without understanding where you are, and where you want to be.

That is the first step. Perhaps your lipid levels are already extremely good…

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#11

Interesting. I raise my hand to provide a datapoint of contrary preference. I much prefer a home gym, and have extensive experience of both. In the late 70’s, throughout 80’s and early 90’s I was a regular gym goer. Always hated it. First, I hated the commute, even when, in the late 80’s I lived in luxury building complex with an extremely well equipped gym (Marina del Rey), so just a few minutes leisurely walk. I prefer - vastly - my dedicated home gym, with virtually zero commute. I didn’t like waiting for machines, looking at other people, interacting with the staff, the lockers, hated all of it. There are some gyms around where I live, but they’re the trendy fraudulent (in my eyes only!) kind where they charge you for the space where you can orange theory or crossfit or some other fad and have virtually no machines of any kind. Sometimes I think I could use a dedicated machine for isolating, say, the hip flexor, but as it’s just short term for injury recovery purposes (or like now, for PT connected to my ACDF recovery), so I’m not about to purchase such a machine for my home gym and crowd it with more equipment since it’s a limited time horizon thing. That’s where a commercial gym might be called for, except, like I said the gyms around me are virtually devoid of machines, just spaces filled with bike spinning or treadmills or just ropes, tires and such doodahs, and I’m not about to communte to another county in search for a decently equipped gym. So, at this point I have zero use for a gym. Meanwhile I have no problem with motivation to exercise at my home gym - I hate exercise, so I was forced to, long ago to figure out the whole “motivation” thing. I’ve always hated exercise, but regular as clockwork, I’ve been exercising since my early 20’s - for the one single solitary reason HEALTH. My “trick” is simple. I just tell myself, exercise is nonnegotiable, the question “should I today” never comes up, as I know, “it’s like brushing teeth - you just DO IT”, the moment you start negotiating internally with yourself, it all falls apart. I am extremely rigid for this reason - because even now, decades later, if I relax for one second, I’m in for a giant fight with my exercise hatred. As a result I usually horrify my wife (and recently my surgeon), when I insist on exercising (even if at a lower intensity level) regardless if I’m sick as a dog, injured or whatnot, I’m out jogging in a downpour or in my home gym. Nonnegotiable. Like I answer my wife as to “why I torture myself this way if I don’t enjoy it”, I say “of course I don’t enjoy it, I’m not doing it for my health, you know!”… I never get tired of that joke/cringe/.

Hate gyms. Exercise dutifully at home. One data point. YMMV.

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#12

Do you even have soft plaque that can calcify at 23 yo? Preventing soft plaque is valuable. Stabilizing soft plaque by calcification is as well? Calcified plaque is late stage finding and advanced cardiovascular disease.

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#13

:rofl: :rofl: :rofl: :rofl:; Me thinks you need and extensive lithium orotate intervention.

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#14

I resonate with Cronos Tempi about not liking the gym. Don’t like the music always playing, too loud, even in the locker rooms. Don’t really like anything about it. But I go twice a week to swim in the pool and use the whirlpool and sauna. These are my “Zone 2” days, and a break from using the Peloton and the weights and other stuff I have at home. The thing about the gym is, I have to be there early, ready to get into the water at 8:30, right when the lifeguard break ends, in order to be sure to get a lane. I’m out of there by 10:30. Other days I find all kinds of stuff to do and don’t get into the home gym til 11:30 or later. I’m disciplined enough to work out just about every day, but not disciplined enough to do it productively, on a strict schedule, or long enough, or hard enough. The perfect is the enemy of the good. I forgive myself.

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#15

I have cool state of the art modern workout systems like Beyond Power VOLTRA I units that allow more efficient workouts modes not possible with weight based equipments. I’m pretty sure these are not available in most commercial gyms.

Even my Wahoo KICKR RUN treadmill is much better than what is found in most gyms.

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#16

I just read that study you shared about how lower LDL-C levels are associated with a higher risk of incident T2D , with participants in the low LDL-C group having the highest risk. I’m glad I now have a reason not to take Bempedoic Acid and Ezetimibe. I was a bit worried about falling behind since I’d never heard of those two drugs being used for anti-aging before.Thanks a lot.

#17

Wow. This is completely new to me. That’s the danger of being an old geezer (moi, 67yo), your knowledge of workout equipment stops at what you saw at a gym 30 years ago. You fall into old workout habits you never revise. As an example, only recently was I made aware of electric muscle stimulation suits, and purchased one from VisionBody, which I will start using soon for PT recovery after my recent ACDF surgery. Now this - I’ll have to explore the Voltra and see if it’s a good addition to my home gym. There are not enough hours in the day to keep on top of everything new in every tech area, so thank you for making this geezer aware of what’s out there!

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#18

Some of the things you can do with VOLTRA is power training, which is not really possible with weights. That’s a very interesting feature because power is what declines the most with age.

Key Trends in Declines Over 60:

  • Muscle Power (Explosive Strength): Declines at the fastest rate, often exceeding 3%–4% annually.
  • Muscle Strength (Maximal Force): Declines by roughly 1.5% to 3% per year, often driven by the loss of muscle quality rather than just size.
  • Muscle Mass (Size): Declines at a slower rate of about 1%–2% per year.

When I tried a power push with 10kg I got 300W, when my 33 yo son tried he got 900W but after 3 weeks I was at 500W!

Other cool modes are isometrics and isokinetic. Isometrics RFD (Rate of Force Development) training is extremely safe and efficient for building power through neuromuscular adaptations.

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#19

maybe that’s why people take K2? I have been on statins since 1990. I’m 67,male. My CAC last yr was 42. Not great, and i was hoping for 0 :slight_smile: but not bad either. I’m ok with that score as I have hereditary high levels that diet doesn’t really help. I started taing K2 about 6 months ago. also started taking nattokinase and will have another CAC in 3 yrs to see if there are any significant changes (to the good hopefully)

#20

To be fair to vitamin k2, again, vitamin supplementation isn’t uniform. The type of vitamin, its bioavailability and how natural it is to the body is highly important IMO

I think they were all using the same type of vitamin k2 supplement in that study which may have been synthetic garbage? Or maybe not. We’ve seen these reports with various vitamin D studies IMO

I think it’s important to take the best supplements.